Despite the relative success of cancer chemotherapy side effects remain a major problem. The skin is a major site of several unpleasant side effects of antitumor quinone such as adriamycin. Extravasation during intravenous infusion, which occurs in up to 6% of cancer patients, can produce painful indolent ulcers and, if deepter structures are involved, loss of joint mobility. Treatment of extravasation is largely empirical and no controlled studies have been conducted to determine its effectiveness. Antitumor quinones are known to form free radicals. We reasonsed that it might be possible to protect against the ulcerogenic effects of antitumor quinones by toipical application of lipid soluble free radical scavenging agents. Preliminary studies have shown that topical application of alpha-tocopherol (TS) in dimethylsulfoxide (DMSO) produces over a 70% decrease in ulcer diameter by intradermal adriamycin in rat. This exceeds protection reported for any other treatment. We propose to determine the formulation(s), dose and schedule of TS and DMSO which provide maximum protection against ulceration in rat and pig. We will study protection by other scavenging agents, other vehicles for applying these agents and protection against ulceration by other antitumor drugs. TS and DMSO protect against adriamycin induced hair loss in rat. Alopecia is an emotionally traumatic side effect of chemotherapy for many cancer patients. We will study protection against hair loss produced by systemic adiamycin in guinea pig which resembles man in its pattern of hair growth. Another complicatin of adriamycin chemoctherapy in skin is enhanced sensitivity to radiation. Even without chemotherapy many patients experience unpleasant skin reactions to radiation. Since the primary mechanism of radiation toxicity to skin is through free radicals topical DMSO and TS might prevent some of these complications. We will study absorption of TS and DMSO through skin and mechanisms for the increased toxicity of adriamycin in the presence of TS esters. The ultimate objective of our studies is to acquire knowledge of mechanisms of anticancer durg skin toxicity and develop ways of treating skin toxicity which might be effective in humans.